"Quadruple whammy"- a preventable newly described syndrome of post-operative AKI in CKD II and CKD III patients on combination "Triple whammy" medications: a Mayo Clinic Health System, Eau Claire, Wisconsin experience.

BACKGROUND: The potential combination of diuretics- angiotensin-converting enzyme inhibitors- Non-steroidal anti-inflammatory drugs (diuretics-ACEIs-NSAIDs), the so-called 'triple whammy', to produce clinically significant nephrotoxicity in chronic kidney disease (CKD) is often unrecognized. In 2013, in the British Medical Journal, we described accelerated post-operative acute kidney injury (AKI) in CKD patients concurrently on 'triple whammy' medications, a new syndrome that we aptly named 'quadruple whammy'. MATERIALS AND METHODS: Two case reports. RESULTS: I. A 59-year-old Caucasian male, hypertensive CKD III, serum creatinine (SCr) 1.42 mg/dL, developed accelerated oliguric AKI after elective right nephrectomy. Outpatient medications included Lisinopril-Hydrochlorothiazide and Nabumetone (NSAID). SCr rapidly more than doubled with metabolic acidosis and hyperkalemia within 24 hours, peaking at 4.02 mg/dL. 'Triple whammy' medications were promptly stopped and the hypotension was corrected. SCr was 1.64 mg/dL and stable, after three months. II. A 46-year-old Caucasian male, hypertensive CKD II, SCr 1.21 mg/dL, developed accelerated AKI after elective right hip arthroplasty. Outpatient medications included Lisinopril and Hydrochlorothiazide. Celecoxib (200 mg) was given pre-operatively. Within 36 hours, SCr rapidly more than doubled to 2.58 mg/dL, with metabolic acidosis. 'Triple whammy' medications were promptly stopped and the hypotension was corrected. SCr was 0.99 mg/dL, and stable, after one month. CONCLUSION: We have described two cases of preventable accelerated AKI following post-operative hypotension in CKD patients concurrently on 'triple whammy' medications. We dubbed this new syndrome "Quadruple Whammy". It is not uncommon. 'Renoprevention', the pre-emptive withholding of (potentially nephrotoxic) medications, including 'triple whammy' medications, pre-operatively, in CKD patients, together with the simultaneous avoidance of peri-operative hypotension would help reduce, if not eliminate such AKI - a call for more pharmacovigilance.

Too much coronary angioplasty in the USA?: less may be better - the conflicting roles of inexactness of medicine as a science, asymmetric information, technologic imperative, unnecessary care and ethicomedicinomics in US healthcare.

US healthcare expenditure per capita far exceeds that of any other nation in the world. Indeed, over the last 15 years, the USA has distantly surpassed most countries in the developed world in total healthcare expenditures per capita with the USA now spending 17.4% of its gross domestic product (GDP) on healthcare ($7960 per capita), compared with only 8.5% of GDP in Japan ($2878 per capita), a distant second. Consequently, by current projections, the US healthcare bill will have ballooned from $2.5 trillion in 2009 to over $4.6 trillion by 2020. Such spending growth rates are unsustainable and the system would soon go broke if not corrected. The drivers of these spending growth rates in US healthcare are several and varied. Indeed, in September 2012, the Institute of Medicine reported that US healthcare squandered $750 billion in 2009 through unneeded care, Byzantine paperwork, fraud and other wasteful activities. Recently, the question was raised as to whether we have too much coronary angioplasty in the USA. In this analysis, we examine these and other various related aspects of US healthcare, make comparisons with other national healthcare delivery systems, and suggest several reengineering modalities to help fix these compellingly glaring glitches and maladies of US healthcare.

Syndrome of rapid onset end stage renal disease in incident Mayo Clinic chronic hemodialysis patient.

Despite decades of research, a full understanding of chronic kidney disease (CKD)-end stage renal disease (ESRD) progression remains elusive. The common consensus is a predictable, linear, progressive and time-dependent decline of CKD to ESRD. Acute kidney injury (AKI) on CKD is usually assumed to be transient, with recovery as the expected outcome. AKI-ESRD association in current nephrology literature is blamed on the so-called "residual confounding." We had previously described a relationship between AKI events and rapid onset yet irreversible ESRD happening in a continuum in a high-risk CKD cohort. However, the contribution of the syndrome of rapid onset-ESRD (SORO-ESRD) to incident United States ESRD population remained conjectural. In this retrospective analysis, we analyzed serum creatinine trajectories of the last 100 consecutive ESRD patients in 4 Mayo Clinic chronic hemodialysis units to determine the incidence of SORO-ESRD. Excluding 9 patients, 31 (34%) patients, including two renal transplant recipients, had SORO-ESRD: 18 males and 13 females age 72 (range 50-92) years. Precipitating AKI followed pneumonia (8), acutely decompensated heart failure (7), pyelonephritis (4), post-operative (5), sepsis (3), contrast-induced nephropathy (2), and others (2). Time to dialysis was shortest following surgical procedures. Concurrent renin angiotensin aldosterone system blockade was higher with SORO-ESRD - 23% versus 5%, P = 0.0113. In conclusion, SORO-ESRD is not uncommon among the incident general US ESRD population. The implications for ESRD care planning, AV-fistula-first programs, general CKD care and any associations with renal ageing/senescence warrant further study.

Syndrome of rapid-onset end-stage renal disease in two consecutive renal transplant recipients.

A syndrome of rapid-onset end-stage renal disease (SORO-ESRD) following acute kidney injury (AKI) in native kidneys was described recently. To what extent this syndrome of unanticipated and rapidly irreversible ESRD impacts renal allograft survival is unknown. Over 6 months, we managed two deceased donor renal transplant recipients (RTRs) with rapid acceleration of previously stable allograft chronic kidney disease to abruptly terminate in irreversible ESRD following AKI. These are the first reports of SORO-ESRD in RTRs. More research is needed to ascertain the contribution of SORO-ESRD to renal allograft loss.

Reno-prevention vs. reno-protection: a critical re-appraisal of the evidence-base from the large RAAS blockade trials after ONTARGET--a call for more circumspection.

The ACEI, captopril was introduced into clinical medicine in the early 1970s for hypertension. Other ACEIs and the ARBs were introduced subsequently. Following several RAAS blockade trials, we now have an expanded set of clinical indications for these agents. Despite the escalated use of these agents, we continue to experience an unexplained epidemic of ESRD/CKD/ARF. There are concerns regarding potential iatrogenic renal failure arising from these agents. A case, it would appear, of unintended consequences. Our publication of several reports on the previously unrecognized syndrome of late onset renal failure from angiotensin blockade (LORFFAB) in 2008 adds to this evolving literature. At the same time, some recent reports have questioned the veracity of claims of superior reno-protection with these agents beyond BP lowering. A post hoc analysis of a subset of patients in the MICRO-HOPE cohort suggested that a previously unrecognized greater 24-h BP lowering achieved in the ramipril arm vs placebo could explain the reported benefits of the ACEI. These doubts and concerns became heightened by the results of the ONTARGET study. Our critical re-appraisal of the large RAAS blockade trials revealed design flaws and protocol contradictions that further these doubts and concerns. We conclude that these agents be used more judiciously, with better monitoring of kidney function. Treating physicians must consider drug discontinuation in selected patients. We also support temporary withdrawal of these agents before major surgical procedures, contrast media administration and during acute illness. Such preventative measures (reno-prevention) would enhance the benefits of reno-protection with RAAS blockade.

Worsening renal failure in older chronic kidney disease patients with renal artery stenosis concurrently on renin angiotensin aldosterone system blockade: a prospective 50-month Mayo-Health-System clinic analysis.

BACKGROUND: The current US chronic kidney disease (CKD)/end stage renal disease (ESRD) epidemic, coincident with the increasing application of renin angiotensin aldosterone system (RAAS) blockade, has raised concerns of iatrogenic renal failure. The US population is an ageing one, further raising the possibility of increasing renal artery stenosis (RAS) in our patients. Current literature regarding worsening renal failure in CKD patients with RAS is based almost wholly on retrospective studies, and therefore may be poorly understood. AIM: To prospectively examine the syndrome of worsening renal failure in CKD patients with hemodynamically significant RAS concurrently on RAAS blockade. DESIGN: Prospective cohort study. METHODS: Between September 2002 and February 2005, CKD patients, concurrently on RAAS blockade, with RAS >70% by magnetic resonance angiography, who presented with accelerated azotemia (> or =25% increase in baseline serum creatinine) were consecutively enrolled. In addition to standard nephrology care, RAAS blockade was discontinued and renal percutaneous transluminal angioplasty (PTA)/stenting performed according to standard guidelines. Renal function as measured by MDRD-derived eGFR (estimated glomerular filtration rate) was monitored. RESULTS: Twenty-six Caucasian patients were enrolled-M:F = 10:16, mean age 75.3 years. Prior duration of RAAS blockade was 20.2 months. Known risk factors were absent in 15/26. Unilateral RAS with dual kidneys was common-19/26. Five patients, with higher baseline creatinine-2.1 +/- 0.6 vs. 1.5 +/- 0.4 mg/dl, P = 0.013, progressed to ESRD; 4/5 ESRD patients died after 6.3 months. Excluding the 5 with ESRD, and 2 lost to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 to 39.7 +/- 14.9 ml/min/1.73 m(2) BSA (P = 0.001), 26.4 months after stopping RAAS blockade. In these same 19 patients, mean arterial blood pressure improved from 100 +/- 9 to 92 +/- 10 mmHg, with 8 patients requiring additional antihypertensive substitutions. Renal PTA/stenting further improved eGFR in 7/9 patients. CONCLUSION: Contrary to previous retrospective reports, we observed that renal failure/ESRD in this older CKD patient population is common in patients with unilateral RAS lesions with dual kidneys; precipitating risk factors are often absent, and progression to ESRD with increased mortality is not infrequent. Older age, higher baseline creatinine (>2.0) and/or lower eGFR (<35) predicted ESRD. eGFR improved following discontinuation of RAAS blockade, generally. Furthermore, in selected patients, renal PTA and stent placement led to additional improvements in eGFR. Our observations call for further studies.

Hepatoma in pregnancy.

We present the third case of hepatoma in pregnancy to be reported in an African. Despite the high incidence of hepatoma in the male population, hepatoma complicating pregnancy is very rare in this environment. Death usually occurs within one year of onset of symptoms. The clinical features during pregnancy do not differ appreciably from its presentation in the non-pregnant state. However, after pregnancy, as demonstrated in our case, the disease appears to pursue a more rapid course. These observations lend more weight to suggestions of a hormonal dependence of hepatoma.

Tropical splenomegaly syndrome in Nigerian adults.

Thirty-nine Tropical Splenomegaly Syndrome (TSS) patients. 19 males and 20 females, aged 13 to 69 years, with a mean age of 44.4 years, seen over a two-year period, January 1987 to December, 1988, at the consultant Medical Out-patient Clinics of the University of Nigeria Teaching Hospital, Enugu, Nigeria, were retrospectively studied. The aetiopathogenetic basis of the syndrome was briefly reviewed. The implications of the probable extent of this medical problem TSS in the tropics was emphasized. The spectrum of clinical presentation, haematological picture and results of other investigations were reviewed. An attempt was made to possibly distinguish TSS from such other similarly presenting conditions as Hodgkin's Lymphoma, Chronic granulocytic leukaemia and Chronic lymphocytic leukaemia, on clinical grounds and simple laboratory data that can be easily available to the tropical physician. The probable complications of TSS, the ease of treatment and the impressive results of therapy were highlighted. The place of the different antimalarial chemoprophylactic agents in the treatment of TSS was reviewed. Finally, the question of the appropriate duration of therapy for TSS was entertained.

Tropical splenomegaly syndrome in Nigerian adults

Thirty-nine tropical splenomegaly syndrome (TSS) patients were studied between january 1987 and december 1988 at the University of Nigeria Teaching Hospital; Enugu; Nigeria. The aetiopathogenetic basis of the syndrome was briefly reviewed. The implications of the probable extent of this medical problems TSS in the tropics was emphasized. The probable complications of TSS; the ease of treatment and the impressive results of therapy were highlighted. The place of the different antimalarial chemoprophyllatic agents in the treatment of TSS was reviewed. Finally; the question of the appropriate duration of therapy for TSS was entertained

A modality of renal substitution therapy

Dialysis is a process whereby the solute composition of a solution A; is altered by exposing solution A to a second solution B; through a semi-permeable membrane. The mechanisms of solute transport across the semipermeable membrane include diffusion and hydrostatic pressure gradient (ultra-filtration). Additionally; water movement in response to osmotic pressure gradient is also involved

Proptotic panophthalmitis and bilateral supraclavicular lymph node metastases from prostatic carcinoma. A case report and literature review

"The authors describe a 68-year old Nigerian male farmer who had right-sided panophthalmitis in association with proptotic orbital metastasis and bilateral suprachlavicular lymphadenopathy from disseminated prostatic carcinoma. This combination; in one patient; of such unusual features of disseminated prostatic carcinoma as orbital metastasis with panophthalmitis and bilateral ""sign of Troisier""; albeit in the absence of urinary symptoms; to our knowledge; has not been reported previously. The patient showed initial response to diethylstilbestrol administration and had the panophthalmitic right eye eviscerated after antibiotic therapy."